Dichloromethane → (3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol

HRID 535475ノート

反応式

HRID 535475 の反応式
O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:13]1[CH:14]=[N:15][C:16]([C:19]2[CH:20]=[C:21]([CH2:25][OH:26])[CH:22]=[CH:23][CH:24]=2)=[N:17][CH:18]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[N:37][N:38]([CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)[CH:39]=2)O1.ClCCl>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[N:42]1([CH2:41][CH2:40][N:38]2[CH:39]=[C:35]([C:13]3[CH:14]=[N:15][C:16]([C:19]4[CH:20]=[C:21]([CH2:25][OH:26])[CH:22]=[CH:23][CH:24]=4)=[N:17][CH:18]=3)[CH:36]=[N:37]2)[CH2:43][CH2:44][O:45][CH2:46][CH2:47]1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 177499241-(2-Morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 18407952Tripotassium phosphate trihydrateHCID 59484879(3-(5-Bromopyrimidin-2-yl)phenyl)methanol

生成物 1

HCID 58289705(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

7.2 4.25 g (20.0 mmol) of tripotassium phosphate trihydrate and 842 mg (1.2 mmol) of bis(triphenylphosphine)palladium chloride are added to a solution, kept under nitrogen, of 2.65 g (1.0.0 mol) of [3-(5-bromopyrimidin-2-yl)-phenyl]methanol and 3.38 g (11.0 mmol) of 4-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]ethyl}morpholine in 50 ml of 1,2-dimethoxyethane, and the mixture is stirred at 80° C. for 18 hours. Dichloromethane and water are added to the reaction mixture, which is then filtered through kieselguhr, and the residue is washed with dichloromethane. The organic phase is separated off, dried over sodium sulfate and evaporated. The residue is recrystallised from 2-propanot, giving (3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol as yellowish crystals; ESI 366. 7.3 A solution, kept under nitrogen, of 324 mg (0.70 mmol) of (3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol, 131 mg (0.91 mmol) of 6-isopropyl-2H-pyridazin-3-one and 278 mg (1.05 mmol) of triphenylphosphine in 1.4 ml of THF is cooled in an ice bath, and 217 μl (1.056 mmol) of diisopropyl azodicarboxylate are added dropwise. After the reaction mixture has been stirred at room temperature for 2 hours, it is evaporated. The residue is chromatographed on a silica-gel column with dichloromethane/methanol as eluent, giving 6-isopropyl-2-(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one (“A13”) as yellowish crystals; ESI 486;

後処理

  1. filtrationis then filtered through kieselguhr
  2. washthe residue is washed with dichloromethane
  3. customThe organic phase is separated off
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe residue is recrystallised from 2-propanot

出典と根拠

ORDレコード
ord-81cdc3d121364a8ca0aefdbe5a28bd84
出典データセット
uspto-grants-2014_10
特許番号
US08859547B2

反応ノート

読み込み中…